Figure 1. Screenshots of a typical BLAT search. (a) The sequence “GTGCAGATAATTAATAAGAAGCTGGATCTTAGCAACGTCCAGTCCAAGTGTGGCTCAAAGGATAATATCAAACACGTCCCGGGAGGCGGCAGT”was entered into BLAT at the UCSC browser at http://genome.ucsc.edu/. This prompts the appearance of the screen shown; (b) Clicking on “Browser” in panel (a) prompts this screen, which may vary depending on the track selection of the browser. In this particular example, “human mRNAs from GenBank” was selected as a “pack” display mode and the individual variants are visible. The arrow points to an exon that is alternatively spliced, as it is present in some, but not all mRNAs; (c) Clicking on the exon indicated with an arrow gives the information of this particular mRNA. On this page, clicking on “View details of parts of alignment within browser window” (under mRNA/genomic alignment) shows the alignment in the screenshot. The exon is shown in blue upper‐case letters, and the flanking introns in black lower‐case letters.

Figure 2. Screenshots of a SROOGLE analysis. (a) The sequence of tau exon 10 shown in Figure 1 was entered into the “Exon” field of SROOGLE at http://sroogle.tau.ac.il/. The sequence is shown and the AAG trinucleotide sequence that is deleted in a human patient was boxed (not by the program). SROOGLE shows regulatory motifs underneath the sequence; their color is explained in panel (c). The line indicated with a circle‐marked arrow shows values of neighborhood inference. If they are above the straight line, the program predicts enhancers, while below the line are silencers. The line indicated by a diamond‐marked arrow shows the mutability index, which is a measure of how much a change at this position would lead to a decreased number of regulatory sequences overlapping that position; (b) The same analysis was performed for the human mutation that lacks the AAG nucleotides. Note that the enhancer sequences indicated by a pointed arrow disappear, and that the NI values drop slightly (circle‐marked arrow); (c) Color coding of the splicing regulatory elements in the program.